GB1577327A

GB1577327A - Vascular prostheses

Info

Publication number: GB1577327A
Application number: GB1714/77A
Authority: GB
Original assignee: Sumitomo Electric Industries Ltd
Current assignee: Sumitomo Electric Industries Ltd
Priority date: 1976-01-21
Filing date: 1977-01-17
Publication date: 1980-10-22
Also published as: IT1192217B; JPS5737338B2; BE850542A; AU498725B2; JPS5289298A; FR2338691B1; SE428524B; NL164470C; AU2111677A; CA1081403A; DE2702513B2; FR2338691A1; BR7700349A; NL164470B; SE7700601L; NL7700561A; DE2702513A1

Description

(54) VASCULAR PROSTHESES (71) We, SUMITOMO ELECTRIC INDUSTRIES LTD., a Japanese company of No.

15, Kitahama 5-Chome, Higashi-ku, Osaka-shi, Osaka, Japan do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed to be particularly described in and by the following statement: The invention relates to a vascular prosthesis composed of a polytetrafluoroethylene material (as defined herein) and, more specifically, to an artificial blood vessel which is expected to expedite the heating of anastomoses and development of the neointima after a surgical implant operation.

Fabric prostheses composed of a knitted or woven fabric of Dacron or polytetrafluoroethylene having inner diameters that are relatively large are now being utilized, with relatively good results. In particular, good results are generally obtained with vascular prostheses for arteries which have an inner diameter of at least 7 mm. Despite this, few prostheses for small inner diameter arteries are clinically acceptable. In venous applications, small inner diameter prostheses show a low patency rate than in arterial application.

The rate of blood flow in veins is smaller than in arteries, and to prevent thrombosis, it is important to inhibit platelet adhesion to the inner surface of the artificial veins. This requirement is not fully met by presently available artificial veins.

Some tubes made of stretched or expanded polytetrafluoroethylene have been demonstrated to be clinically useful as vascular prostheses for arteries and veins. This is described, for example, in Soyer et al., "A New Venous Prosthesis", Surgery, Vol. 72, page 864 (1972), Volder et al., "A-V Shunts Created in New Ways", Trans. Amer. Soc. Artif.

Int. Organs, Vol. 19, p. 38, (1973), Matsumoto et al., "A New Vascular Prosthesis for a Small Caliber Artery", Surgery, Vol. 74, p. 519 (1973), "Application of Expanded Polytetrafluoroethylene to Artificial Vessels", Artificial Organs, Vol. 1, p. 44 (1972), Ibid., Vol. 2, p. 262 (1973), and Ibid., Vol. 3, 337 (1974), Fujiwara et al., "Use of Goretex Grafts for Replacement of the Superior and Inferior Venae Canal", The Journal of Thoracic and Cardiovascular Surgery, Vol. 67, p. 774 (1974), and Goldfarb, Belgian Patent No. 517,415.

The results of these clinicial experiments are summarized below.

When a suitable porous prosthesis is implanted as a conduit within the arterial system, the fine pores are clogged by clotted blood, and the inside of the prosthesis is covered with the clotted blood layer. The clotted blood layer is made up of fibrin, and its thickness varies according, for example, to the material of the prosthesis, and the surface structure of the prosthesis. Since the thickness of fibrin approaches 0.5 to 1 mm when a knitted or woven fabric of Dacron (Registered Trademark) or polytetrafluoroethylene is used as the prosthesis, success is achieved only with those blood vessels which are not occluded by this increase in the wall thickness by the fibrin layer (that is, arteries having an inside diameter of 5 to 6 mm or more). Generally, knitted or woven prostheses having small inner diameters have not been successful.

A polytetrafluoroethylene tube which has been stretched has a microstructure composed of very fine fibers and nodes connected together by the fibers. The diameters of the fibers vary depending on various stretching conditions, and can be made much smaller than fibers of the knitted and woven fabrics mentioned above.

It has been confirmed clinically that a polytetrafluoroethylene tube having a pore size of from about 2 F to about 30 F (pore sizes below about 2 F are indesirable), a porosity of about 78% to about 92%, a fiber length of not more than about 34 11 (fiber lengths of about 40 11 to about 110 Ft are undesirable), a nodular size of not more than about 20 Kt, and a wall thickness of about 0.3 mm to about 1 mm exhibits a high patency rate without substantial occlusion by fibrin deposition.

It has been reported, however, that a venous prosthesis shows a much lower patency rate than an arterial prosthesis, and does not prove to be entirely satisfactory for prosthetic purposes. It has also been reported that, when a vascular prosthesis has too high a porosity, tearing of the prosthesis by the suture used in joining the prosthesis with the vessel of the patient tends to occur.

According to the present invention, there is provided a vascular prosthesis comprising a tube of porous polyetrafluoroethylene material (as defined herein), said tube having (a) a porosity of 70 to 95%, (b) a structure of interconnected fibers, (c) a fiber length of not more than 40 Ft and (d) a structure in which the fibers at the inner surface of the tube have an average diameter of 0.1 to 2 CL and the fibers at the outer surface of the tube have an average diameter of at least twice that.

During the healing process after implantation, the outer surface of the polyetrafluoroethylene tube is first enveloped by the connective tissue and organizes, and afterwards the fibrin layer on the inner surface of the tube organizes. At this time, there is established a continuity of the intimas of the host's vessels with the neointima of the inner surface of the tube, and simultaneously, the fibrin layer is replaced by the fibrous tissue which has entered the tube through the fine pores therein. Furthermore, after a certain period of time, the neointimas at the inner surface are connected firmly to the connective tissue lining the outer wall of the prosthesis, thereby completing the formation of an artery. It is known that this artery formation usually takes about 4 to 6 months. It is known, on the other hand that, with vascular prostheses implanted in veins, the rate of entry of the connective tissue from the periphery thereof is slower than for arterial implantation. Preferably, the pores on the outer surface of the tube are larger than the pores on the inner surface. This increases the rate of entry of the connective tissue from the outer periphery. The smaller size of the pores of the inner surface is believed to reduce the surface stagnation of blood flow, with the result that platelet adhesion is reduced and the amount of thrombus formation at the inner surface decreases, as a result of which the fibrin layer is very thin and the thickness of the neointima on the inner surface is decreased when compared to the thickness of a similarly dimensioned prior art vascular prosthesis.

Furthermore, the connective tissue from the outer periphery is allowed to grow and develop fully and to supply enough nutrient to the neointima formed at the inner surface to prevent calcification in the prosthesis wall that may otherwise occur due to degenerative change with the lapse of time, thus increasing the patency rate of the prosthesis after implantation.

Also according to the present invention, there is provided a process for producing vascular prosthesis of a porous fibrous structure which comprises extruding an unsintered polytetrafluoroethylene material (as defined herein) containing a liquid lubricant as an extrusion aid into a tube, stretching the tube at least in its longitudinal direction and then heating the stretched tube so that the temperature of the outer surface of the tube is at least 327"C, and the temperature of the inner surface of the tube is lower than that of the outer surface.

The term "polytetrafluoroethylene material" as used herein means polytetrafluoroethylene, a copolymer containing, in addition to tetrafluoroethylene monomer, a small amount of one or more other olefin monomers or polytetrafluoroethylene blended with a small amount of one or more other polyolefins of commercially available "fine powder" grades provided that the features and advantages of the invention are not destroyed.

Preferably, the heating is effected so that the temperature of the tube is not greater than 3600C.

In a preferred embodiment, the tube has a pore size of 1 ti to 5 ti at the inner surface and at least 3 Ft at the outside surface. The average fiber diameter at the inner surface is preferably 0.1 to 2 Ft and the average fiber diameter at the outer surface is preferably at least twice that.

Preferably, the prosthesis is formed by stretching (in the longitudinal direction) the tube by 100 to 500% and expanding in the radial direction, followed by the above-described sintcring stcp. of 2() to 2()()cm radiillv. Such a vascular prosthesis has enhanced junction tear strength in the implanting operation, and permits a thin neointima to form on the inner surface of the prosthesis after implantation. The inner cavity is not occluded, and the prosthesis has a high rate of patency. Porosity as described herein is determined by measuring the specific gravity by the method or ASTM D276-72 and the pore size distribution and bubble point as described herein are determined by the method of ASTM F316-70.

In the accompanying drawings: Figure 1 is a schematic sectional view of part of a vascular prosthesis that has been implanted; Figure 2 is a scanning-type electron microphotograph of an inner surface of a vascular prosthesis of polytetrafluoroethylene in accordance with the present invention that has been stretched only in the linear direction; Figure 3 is a scanning-type electron microphotograph of an outer surface of the vascular prosthesis of Figure 2; Figure 4 is a scanning-type electron microphotograph of the inner surface of a similar vascular prosthesis which has been both stretched linearly and expanded radially; and Figure 5 is a scanning-type electron microphotograph of the outer surface of the vascular prosthesis shown in Figure 4.

Turning now to the drawings, in Figure 1 the wall of the prosthesis is shown 8 to 10 months after implantation of the prosthesis in a part of a femoral artery.

The wall 1 of the prosthesis has an inner surface 2 and an outer surface 3, and a neo-intima 4 uniformly covers the inner surface 2. On the other hand, connective tissue 5 composed mainly of a collagen substance adheres firmly to the outer surface 3, and fibroblast growth and capillary formation are observed. The fibroblasts contain a spherical nucleus 10, and are uniformly distributed on the wall 1 as black dots. The wall 1 of the prosthesis is a structure composed of irregularly-shaped fiber interconnection points or "nodes" 9 and fine fibers (not shown) connecting the nodes 9 together.

Figures 2 and 3 are scanning-type electron microphotographs (1,000 x magnification) of the inner surfaces 2 and the outer surface 3, respectively, of the prosthesis. The nodes 9 composed of polytetrafluoroethylene are of generally ellipsoidal shape and are interconnected by a number of fibers 11 which are aligned substantially at right angles to the long-axis direction of the nodes 9. The average diameter of the fibers 11 at the inner surface 2 (Figure 2) of the prosthesis is not more than 1/2 the average diameter of the fibers 11 at the outer surface 3 (Figure 3), and in these photographs, the fibers have a diameter of 0.5 ti to 1.0 F at the inner surface, and 1.0 to 3.0 F at the outside surface.

Figure 4 is a scanning-type electron microphotograph (magnification 400 x) of the inner surface of a biaxially stretched (i.e. linearly and radially) tube of polytetrafluoroethylene in accordance with the present invention. It can be seen from the microphotograph that the nodes 9 and the fibers 11 of the polytetrafluoroethylene are both reduced in dimension. The fibers 11 have a diameter of 0.1 1I to 0.6 C1.

The diameter of the individual fibers under a microscope vary considerably according, for example, to the selection of visual field, and the manner of developing the photograph of a sample. Several hundred fibers appear in each of Figures 2 and 3, and several fibers aligned in a slightly deviating manner in the planar direction overlap and look as if they are one thick fiber. For this reason, in order to determine the average fiber thickness, the diameters of at least 3,000 fibers must be measured on the basis of at least 10 photographs, and then an average value of the diameters calculated. At this time, experts in photographic examination can ascertain relatively easily whether a number of fine fibers are aligned in parallel, or whether they form one coalesced thick fiber. In the case of an assembly of fine fibers, transmission (transparency) increases in the planar direction, and the thickness of the fibers is not perceived. However, a coalesced thick fiber can be clearly detected using scanning-type electron microphotograph as a fiber having a thickness. Hence, in determining the average fiber diameter, fibers aligned in a planar direction and having a small thickness must be excluded from the calculation, and only the diameters of distinguishable fibers must be summed to arrive at the average.

In order to stretch and expand tubes of polytetrafluoroethylene, the methods described in Japanese Patent Publication No. 13560/67 and U.S. Patent 3,953,566 can basically be utilized. For example, about 15 to 40 vol% of a liquid lubricant as an extrusion aid, such as mineral oil, liquid paraffin or naphtha, is mixed with a fine powder (e.g. a powder having a particle size of about 0.1 to about 0.5 11 and a surface area of about 5 to about 15 m2/g) of polytetrafluoroethylene, and the mixture extruded into a tubular form using a ram-type extruder. Any type of polytetrafluoroethylene can be used in this invention and those having a molecular weight of about 2,000,000 to about 4,000,000 are preferred. The tube is then stretched in at least one direction while it is heated at a temperature below the sintering temperature (i.e. about 327"C). Then, while the tube is fixed so that it does not shrink, it is heated to a temperature of at least 327"C to set the stretched and expanded structure and thereby to form a tube having increased strength. Without modifying this procedure, however, a tube in which the fibrous structure at the inner and outer surfaces differs cannot be obtained. In order to obtain such a structure, the tube is externally heated while being forcibly cooled internally to form a temperature gradient across the tube wall with the temperature increasing towards the outside of the tube during the sintering process. For this purpose, the inner surface of the tube is continuously exposed to air at a temperature ranging from room temperature (20 to 30"C) to 3270C by continuously introducing such air into the inside cavity of the tube either forcibly or by a continuous pressure reduction in the inside cavity of the tube in such a manner that the outer surface of the tube is heated to temperatures of at least 3270C. The inner surface may or may not be heated to the sintering temperature. However, the inner surface must always be at a lower temperature than the outer surface during the sintering process.

Expanding of the tube in the radial direction thereof can optionally be performed continuously by reducing the pressure surrounding the tube. This may be performed separately, after linear stretching but before sintering.

Naturally, the number, length and diameter, of fine fibers formed vary depending on the degrees of stretching and expansion in the longitudinal and radial directions respectively, and can be appropriately selected depending on the desired porosity, pore size, softness, and tear strength. When the degress of stretching and expanding are approximately equal, the fine fibers are uniformly distributed radially from spherical nodes, and despite this, the direction of fiber alignment differ between the inner surface and the outer surface of the tube. If either of the linear stretching or radial expanding is carried out to a substantially greater degree for the one than for the other, fine fibers in the direction of higher stretch or expansion are longer and larger in number and the fibers are shorter and fewer in number in a direction at right angles to that direction.

It can be ascertained from electron-microscopic examination that the size of the nodes and the diameter of the fibers in a tube subjected to stretching and expansion in two directions show greater changes than those of a tube subjected to stretching or expansion in only one direction. It can be seen particularly that the fibers are distributed in a more radial direction at the inner surface than at the outer surface of the tube.

With increasing stretch ratio, the size of the nodes decreases progressively. When the tube is stretched in one direction, the nodes have the form of elongated ellipsoids. But after treatment in two directions, the size of the nodes is 1/3 to 1/10 of that after a stretching in one direction, and in many cases, the nodes assume a substantially spherical form.

The diameter of the fibers after stretching in one direction is almost constant at 0.5 to 1 ti regardless of the stretch ratio, but treatment in two directions causes the fibers to decrease in diameter by 1/3 to 1/5 and the number of fibers increases correspondingly.

The temperatures used for stretching, expanding and sintering are described below.

Stretching or expanding treatment causes the tube to attain a dimension and a shape which are different from the dimension and shape before such treatment. At least an external force must be exerted in order to cause this change. Similar to thermoplastic resins, in general, this force tends to be lower at higher tube temperatures and higher at lower tube temperatures. This external force required force required for deformation is comparable to the strength at which the tube itself possesses as a result of being oriented in fibrous form by extrusion. The strength built up by the extrusion-forming depends greatly on the extrusion conditions. When the temperature for deformation of the tube by stretching or expanding is below a certain limit, the external force required for deformation is higher than the strength of the tube, and breakage increases during deformation. On the other hand, when the temperature is above this certain limit, the external force for deformation becomes lower than the strength of the tube, and breakage abruptly decreases. Accordingly, in the deformation of the tube, there is a lower limit to the temperature depending on the extrusion conditions.

The same tendency exists in the rate of deformation by stretching or expanding. When the rate of deformation increases, the external force required for deformation increases.

Thus in order to prevent a breakage of the tube, it is necessary to heat the tube at still higher temperatures.

The minimum temperature for deformation cannot be definitely set forth because the strength of the tube varies depending on the tube extruding conditions. Those skilled in the art, however, can easily determine the minimum deformation temperature.

The sintering step comprises heating e.g., until completely melted, of a uniaxially stretched tube, or stretched and biaxially expanded tube to a temperature of at least 3270C while the tube is fixed so that shrinkage does not occur. A difference in the porous fibrous structures of the inner and outer surfaces of the tube can be achieved by heating the outside of the tube while cooling the inner surface of the tubing by passing air through the tube. By increasing the amount of air passed through the cavity of the tube or by reducing the temperature of the air, it is possible to heat the outer surface of the tube to a temperature of at least 327"C whilst at the same time maintaining the inner surface of the tube at a temperature below 327"C. In such a tube, only the outer surface is sintered, and the inner surface remains unsintered. Thus, the shapes and sizes of the fibers and nodes differ greatly between the inner surface and the outer surface. Alternatively, the inner surface of the tube can be heated to a temperature of above 327"C by decreasing the amount of air passed through the interior of the tube or increasing the temperature of the air. This can also be accomplished by increasing the length of the heating zone or increasing the heating zone temperature. As a result, fibers at the outer surface of the tube are exposed to a temperature of greater than 327"C for long periods of time, and while initially they have the same structure (particularly diameter) as those at the inner surface, they gradually become thicker as a result of coalescence. For example, four fibers are fused and coalesced together to form a single fiber having a diameter twice that of each single fiber before sintering.

The thickness of the inner surface structure becomes different from that of the outside surface structure by changing the amount of cooling air passed through the interior of the tube and the amount of heat supplied externally. Increasing the amount of external heat supplied results in an increase in the outer wall thickness of the thicker fibrous structure diameter or large pore size, and if the amount of cooling air is increased, the inner wall thickness of the inner fibrous diameter or small pore size increases. In this case, however, the size of the nodes does not change, and therefore, the size of the nodes at the outer surface is substantially the same as that of the nodes at the inner surface.

As shown in Figure 4, when a longitudinally stretched tube is further expanded in its radial direction, the size of the nodes 9 and the diameter of fibers 11 change drastically.

The nodes 9 in Figures 2 and 3 are ellipsoidal and have a relatively uniform size. But in the biaxially stretched and expanded tube nodes 9 formed as a result of uniaxial stretching are divided into smaller portions depending on the degree of expansion, and fibers 11 occur among the separated nodes. The fibers 11 in Figure 2 or 3 have a diameter of approximately 0.5 to 2 , although the diameter varies somewhat depending on the condition of tubing preparation. However, the fibers 11 after stretching and expanding biaxially as in Figure 4 have a diameter of 0.1 11 to 0.5 y. As a result of expansion biaxially, the diameter of the fibers 11 between the nodes 9 becomes 1/3 to 1/5 of that of the fibers of a tube that has been stretched only uniaxially. Consequently, a single fiber 11 that occurs after the uniaxial expansion is again divided into 10 to 30 fine fibers as a result of the second, radial expansion.

Figure 4 shows the inner surface fibrous structure biaxially expanded tube. Just as in the relation between Figures 2 and 3, the fibers at the outer surface attain a diameter at least twice that of the fibers at the inner surface by sintering the tube while forcibly cooling the inner surface.

The fiber alignment of the inner surface can be made drastically different from that of the outer surface by increasing both the amount of cooling air passed through the tube and the amount of heat supplied externally. An example is shown in Figure 4 (inside surface) and Figure 5, (outside surface).

The fibrous structure at the outer surface of the tube is less dense than that of the inner surface, but each fiber is thicker and this produces various effects as described below.

Firstly, this serves to increase the mechanical strength of vascular prostheses made of such a tube whereby preventing a suture from tearing the prosthesis in the longitudinal direction during implant surgery. It is possible for only the inner surface fibrous structure of the tube to act as a bag-like receptacle for transporting blood. But for application to arteries, the tube must withstand a blood pressure of about 120 mmHg, and should not be compressed by elastic fibroblasts that develop on the outer periphery thereof. In addition, the tube must withstand suturing at the time of surgical operation. The force required to cut the fibers can be increased by increasing the diameters of the fibers at the outer surface of the tube and increasing the number of fibers that are aligned at right angles to the direction of possible tearing. In particular, a tube that has been biaxially stretched and then sintered to increase the fiber diameter has improved tear strength.

Secondly, as a result of decreasing the dimension of the fibrous structure at the inside surface of the vascular prosthesis made of the polytetrafluoroethylene tube, its surface resistance to flow of blood is reduced, and consequently, platelet adhesion is reduced.

Platelets which have contacted the surface of the prosthesis and adhered thereto aggregate reversibly with adenosine diphosphate and calcium ions, after which they become -irreversibly adhered and form a thrombus together with fibrin. The thrombus layer becomes thinner as the amount of platelets that have adhered decreases. The thickness of the initial thrombus layer increases as the fibrin deposits onto it, and this finally causes occlusion. In order, therefore, to obtain vascular prostheses free from occlusion, it is essential to decrease the thickness of the initial thrombus layer. This effect is more pronounced in veins than in arteries. In other words, a reduction in the thickness of neo-intimas on the inner surface of the prostheses can be expected.

As a third effect, fibroblasts rapidly enter the prosthesis from the outer periphery of the prosthesis and grow fully as a result of the increase in the size of the openings in the outer surface fibrous structure of the prosthesis. It is already known that fibroblasts readily enter a vascular prosthesis made of a knitted or woven fabric or Dacron (R.T.M.), or polytetrafluoroethylene, etc., because such a prosthesis has a tubular wall of a loose structure. However, bleeding occurs through the wall immediately after implantation and this results in an increase in the thickness of the fibrin layer on the inner surface of the prosthesis. Further increase leads to calcification and occlusion. In a prosthesis made of polytetrafluoroethylene having the same fibrous structures at the outer and inner surfaces it is essential to decrease the thickness of the fibrin layer that results from platelet adhesion by making the pore size sufficiently small to prevent bleeding and therefore, the ease of entry of fibroblasts from the outside of the prosthesis must be sacrificed somewhat.

When the fibrous structure differs between the outer surface and the inner surface of a prosthesis as defined by its fiber diameter i.e. the spaces between the fibers, or pores, at the outside surface being at least twice that at the inner surface, as in the present invention, the thickness of the fibrin layer at the inner surface can be decreased, and at the same time, entry of fibroblasts from the periphery can be facilitated. Furthermore, nutrient supply to the neo-intimas occurring at the inner surface of the prosthesis can be effected sufficiently through capillaries which densely develop on fully grown fibroblasts. Thus it is possible to greatly reduce calcification of the neo-intimas that may result from nutritional deficiency.

In arterial prostheses, nutrition can be effected not only through capillaries at the fibroblasts, but also from the blood within the cavity of the prostheses. However, in venous prostheses nutrition from the blood can hardly be expected, and reliance must be exclusively on the capillaries present on the fibroblasts that have come through the outer periphery for nutrient supply. Accordingly, the entry of fibroblasts from the outer periphery of vascular prostheses is important not only for the formation of neo-intemas, but also for preventing calcification of the neo-intimas which may be caused by a nutritional deficiency after implantation and thereby for increasing the patency rate of the prosthesis after operation. This is more important in venous prostheses.

The relation between the mean pore size and the length and diameter of fibers among the nodes in a microstructure consisting of very fine fibers of polytetrafluoroethylene and nodes connected to one another by the fibres is described below.

If the length of each fiber connecting nodes is e and the distance between two fibers is d, then the sectional surface of rectangle surrounded by the two fibers and the nodes has the following relation with regard to the fluid dynamical equivalent pore size y.

2Iy = lie + 1/d Since e is usually far larger than d, y becomes approximately equal to 2d. Ultimately, the structure can be described as a porous structure having a fluid dynamical equivalent pore size which is twice the interfiber distance. It is believed that the number of fibers occurring between two nodes is approximately the same for both the ou tubular wall of the prosthesis by the suture during a suturing operation can occur.

Prostheses having a porosity of more than 96% are not practical, and those having a porosity of less than 60% have a short fiber length and prevent entry of fibroblasts after implantation.

The most preferred porosity is within the range of 70% to 95%. It has been clinically confirmed that the preferred range somewhat differs between arterial prostheses and venous prostheses.

As described hereinabove, the fiber length is proportional to the porosity, and prostheses defined by a fiber length of less than about 40 > are preferred in this invention.

Another significant factor for growing neo-intimas on the inside surface of prostheses and preventing them from degeneratively changing with time is the thickness of the tubular wall of the prostheses. With prostheses comprising a fibrous structure only at the inside surface, there is a certain limit to the distance through which fibroblasts enter the prostheses from the outer surface. Consequently, the distance over which nutrient is supplied is also limited.

It has been found clinically that the maximum thickness of the tubular wall is about 0.8 mm.

In the present invention, the wall thickness of the fibrous structure at the inner surface and that of the fibrous structure at the outer surface can be varied depending on the conditions of preparation of the tube. For example, by adjusting the thickness of the inner surface layer to 0.4 mm and the outer surface layer to 0.4 mm, the distance of fibroblast entry can be adjusted substantially to 0.4 mm.

The prostheses defined by the properties described hereinabove serve to facilitate the suturing technique in operation and expedite the healing of patients after operation. Since neo-intemas are maintained free from degenerative change with their use, occlusion does not occur. Accordingly, the prostheses in accordance with this invention contribute greatly to not only surgery but also to industry.

The following example is given to illustrate the invention in greater detail.

Example 2 kg of a commercially available polytetrafluoroethylene (TEFLON .6, a Registered Trade Mark for a product of E.I. du Pont de Nemours & Co.) and 0.52 kg of a white oil (Sumoil P-55, a Registered trademark for a product of Muramatsu Sekiuo Kabushiki Kaisha) were mixed, and the mixture was formed into a tube having an inside diameter of 4 mm and an outside diameter of 6 mm using a ram-type extruder. The tube was then heated to a temperature below the boiling point of the white oil (i.e. 180 - 250"C) to remove the white oil. The tube (20 cm long) was rapidly stretched to a length of 100 cm while being heated at 2000C. The stretched tube was anchored at both ends to prevent shrinkage. At the same time, a pipe for introducing a cooling air was connected to one end of the tube and the other end was sealed. The tube was placed in a furnace and the temperature of the furnace was gradually increased. When the temperature reached 320"C, air (at 200"C) at a pressure of 0.4 kg/em of 0.4 kg/cm2 was abruptly introduced, and while maintaining the air at this pressure and at the temperature of 200"C, the temperature of the furnace was increased to a maximum temperature of 440"C. After confirming the temperature was 440"C, the tube was rapidly cooled to room temperature (about 20 - 30"C).

The inner and outer surfaces of the resulting tubing were photographed using a scanning type electron microscope (1,000 x) and the microphotographs obtained are shown in Figures 2 and 3. It was determined that the fiber diameter was 0.5 to 1.0 11 at the inner surface and 1.0 to 3.0 ss at the outer surface. The fiber length was 15 to 30 > both at the inner and outer surfaces. The tube as a whole had a porosity of 81%.

For comparison, a tube was produced under the same conditions as set forth above except that air was not introduced into the inside cavity of the tube. The resulting tube had a similar structure to that illustrated in Figure 2 at the inner and outer surfaces, but the porosity had decreased to 76%. The pore size of the tube in this comparison was measured, and it was found that its bubble point determined using isopropyl alcohol (according to ASTM F316-70) was 0.15 kg/cm2, and its mean pore size according to (ASTM F316-70) was 2.5 ti. Hence, the comparison tube was believed to have much the same pore size as the inner surface of the tube shown in Figure 2.

It was impossible on the other hand to measure directly the pore size of the inner surface in Figure 3. From the fiber Diameter and the interfiber distance determined from Figure 3, the mean pore size of the outer surface was believed to be about four times (i.e. about 7 ) that of the inner surface.

The tube stretched to five times its unstretched length at 200"C as described above was connected to a pipe for supplying cooling air. When the temperature of the furnace became 325"C air at the pressure of 0.9 kg/cm2 was introduced. The tube was thus expanded to an outside diameter of 8 mm. After increasing the temperature of the furnace to a maximum of 480"C the tube was rapidly cooled. The fiber diameter of the resulting tube was 0.4 to 0.8 ti at the inner surface and 1 to 3 p at the outer surface and the tube as a whole had a porosity of 89%.

Air at a pressure of 1.5 kg/cm2 was introduced into the tube stretched to five times its unstretched length at 200"C as described above when the furnace temperature reached 330"C. This resulted in increase in the outside diameter of the tube to 16 mm. The air pressure was reduced to 0.4 kg/cm2, and the furnace temperature was increased to 4650C at the highest, after which the tube was rapidly cooled. The inner surface of the resulting tube was shown in Figure 4. The fiber diameter of the inner surface was 0.1 to 0.2 ti, and the tube as a whole had a porosity of 93%.

Attention is drawn to the Specification and claims of our copending British Patent Application No. 53991/76 (Serial No. 1577326).

WHAT WE CLAIM IS: 1. A vascular prosthesis comprising a tube of porous polytetrafluoroethylene material (as defined herein), said tube having (a) a porosity of 70 to 95%, (b) a structure of interconnected fibers, (c) a fiber length of not more than 40 ti and (d) a structure in which the fibers at the inner surface of the tube have an average diameter of 0.1 to 2 ti and the fibers at the outer surface of the tube have an average diameter of at least twice that.

2. A vascular prosthesis as claimed in claim 1, wherein the fibers at the inner surface are distributed more radially than the fibers at the outer surface.

3. A vascular prosthesis as claimed in claim 1 or 2, wherein the fibers are interconnected by generally ellipsoidal formations, the length of the long axis of each ellipsoidal formation at the outer surface being at least twice that of the long axis of each ellipsoidal formation at the inner surface.

4. A vascular prosthesis as claimed in any preceding claim, wherein the pores on the outer surface are larger than the pores on the inner surface.

5. A process for producing a vascular prosthesis of a porous fibrous structure, which comprises extruding an unsintered polytetrafluoroethylene material (as defined herein) containing a liquid lubricant as an extrusion aid into a tube, stretching the tube at least in its longitudinal direction and then heating the stretched tube so that the temperature of the outer surface of the tube is at least 327 C, and the temperature of the inner surface of the tube is lower than that of the outer surface.

6. A process for producing a vascular prosthesis of a porous fibrous structure which comprises extruding an unsintered polytetrafluoroethylene material (as defined herein) containing a liquid lubricant as an extrusion aid into a tube, stretching the tube at least in its longitudinal direction and then radially expanding the stretched tube while heating the same so that the temperature of the outer surface of the tube is at least 3270C, and the temperature of the inside surface of the tube is lower than that of the outer surface.

7. A process as claimed in claim 6, wherein the inner surface as claimed in claim 6, wherein the inner surface is not heated to a temperature of 327"C or higher.

8. A process as claimed in claim 5, 6 or 7, wherein the pressure outside the tube is reduced when the tube is heated.

9. A process as claimed in claim 5, 6 or 7, wherein the tube is heated externally and cooling air is passed through the interior of the tube.

10. A vascular prosthesis as claimed in claim 1 substantially as hereinbefore described in the accompanying example or with reference to the accompanying drawings.

11. A process as claimed in claim 5, substantially as hereinbefore described in the accompanying example.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims

**WARNING** start of CLMS field may overlap end of DESC **. at the inner surface and 1 to 3 p at the outer surface and the tube as a whole had a porosity of 89%. Air at a pressure of 1.5 kg/cm2 was introduced into the tube stretched to five times its unstretched length at 200"C as described above when the furnace temperature reached 330"C. This resulted in increase in the outside diameter of the tube to 16 mm. The air pressure was reduced to 0.4 kg/cm2, and the furnace temperature was increased to 4650C at the highest, after which the tube was rapidly cooled. The inner surface of the resulting tube was shown in Figure 4. The fiber diameter of the inner surface was 0.1 to 0.2 ti, and the tube as a whole had a porosity of 93%. Attention is drawn to the Specification and claims of our copending British Patent Application No. 53991/76 (Serial No. 1577326). WHAT WE CLAIM IS:

1. A vascular prosthesis comprising a tube of porous polytetrafluoroethylene material (as defined herein), said tube having (a) a porosity of 70 to 95%, (b) a structure of interconnected fibers, (c) a fiber length of not more than 40 ti and (d) a structure in which the fibers at the inner surface of the tube have an average diameter of 0.1 to 2 ti and the fibers at the outer surface of the tube have an average diameter of at least twice that.